Array comparative genomic hybridization analysis of solid pseudopapillary neoplasms of the pancreas

Abstract

Solid pseudopapillary neoplasms of the pancreas are low-grade malignancies, but their biological behavior cannot be stratified solely on the basis of histopathologic criteria. Aside from mutations in b-catenin and lack of genetic changes common to pancreatic ductal adenocarcinomas, little is known about the chromosomal alterations in solid pseudopapillary neoplasms. We applied array comparative genomic hybridization to a series of 12 patients. The average age was 31 years (range 12-52 years) with 10 female and 2 male patients. The average tumor size was 7.3 cm (range 2-24 cm) with five lesions greater than 5 cm. All cases had 'bland' cytology without significant pleomorphism or high nuclear grade, but seven cases demonstrated at least one of these potentially aggressive histopathologic features: size 45 cm, tumor necrosis, lymphovascular invasion, perineural invasion and peripancreatic invasion. Clinically, one lesion demonstrated aggressive behavior. By array comparative genomic hybridization, chromosomal losses and/or gains were identified in eight cases; five cases had multiple (five or more) alterations. The most common alterations were gains at 13q, 17q, 1q and 8q. Six of the seven cases with at least one aggressive feature had genetic alterations, while only two cases without adverse features had genetic alterations (P ¼ 0.024). The single clinically aggressive tumor exhibited seven chromosomal gains and four aggressive histopathologic features. Our study demonstrates that genetic alterations detected by array comparative genomic hybridization are common in solid pseudopapillary neoplasms of the pancreas. Additional study and longer follow-up are needed to determine if these genetic abnormalities could help predict clinical behavior in these neoplasms.

Does Computed Tomography Have the Ability to Differentiate Aggressive From Nonaggressive Solid Pseudopapillary Neoplasm?

“…In our cohort, despite the presence of large lymph nodes on imaging, patients did not have metastatic adenopathy, as also seen in a study by Tipton et al [26, 35]. Other studies have also alluded that a formal lymphadenectomy, despite the presence of enlarged lymph nodes, may not be necessary [35, 40, 48, 49].…”

“…Pathologically aggressive tumor features were defined as a diameter of >5 cm, tumor necrosis, invasion into peripancreatic soft tissue, extension into the adjacent fat and lymphovascular/perineural invasion (Fig1) [26]. Tumors which had these pathologic features were considered aggressive and tumors which did not have these features were considered non-aggressive.…”

Recurrence of Solid Pseudopapillary Neoplasms of the Pancreas: Results of a Nationwide Study of Risk Factors and Treatment Modalities

“…In a previous analysis, we identified PDX1 and Sox9 proteins expression in the cytoplasmic compartment of SPPN, favoring the hypothesis that SPPN originated from transformation of quiescent pancreatic stem cells . Analysis of genetic alterations by array comparative genomic hybridization reported several chromosomal abnormalities, such as 13q, 17q, 1q, and 8q gains that positively correlated with more aggressive histologic feature of the tumor . On the contrary, immunohistochemistry failed to demonstrate a link between the expression of MMP‐7, cyclin‐D1, c‐myc, and Ki‐67, and the potential malignancy of SPPN .…”

Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features

“…[41][42][43][44][45][46] MOLECULAR FEATURES AND THEIR LINK WITH THE IMMUNOHISTOCHEMICAL PROFILE AND MORPHOLOGIC CHARACTERISTICS Solid pseudopapillary neoplasms lack alterations in genes commonly found in ductal adenocarcinoma, such as KRAS, TP53, P16/CDKN2A, and SMAD4, and show low prevalence of abnormalities in chromosomes 11q, 13q, 17q, 1q, and 8q. 47,48 The molecular hallmark of SPNs is represented by point mutations in exon 3 of the CTNNB1 gene, which is involved in the Wnt/b-catenin signaling pathway. This genetic alteration is observed in more than 90% of cases.…”